Molecular biomedicine最新文献

Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer. 揭示 Pleckstrin-2 在肿瘤进展和免疫调节中的作用：以肺癌为重点的泛癌症综合分析的启示。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-15 DOI: 10.1186/s43556-024-00225-8

Enzhi Yin, Chengming Liu, Yuxin Yao, Yuejun Luo, Yaning Yang, Xiaoya Tang, Sufei Zheng, Linyan Tian, Jie He

{"title":"Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer.","authors":"Enzhi Yin, Chengming Liu, Yuxin Yao, Yuejun Luo, Yaning Yang, Xiaoya Tang, Sufei Zheng, Linyan Tian, Jie He","doi":"10.1186/s43556-024-00225-8","DOIUrl":"10.1186/s43556-024-00225-8","url":null,"abstract":"Cancer remains a leading cause of mortality globally, highlighting the need for novel biomarkers to enhance prognosis and therapeutic strategies. Pleckstrin-2 (PLEK2), a member of the pleckstrin family, has been implicated in processes critical to tumor progression, but its role across cancers remains underexplored. This study systematically examined the expression patterns, prognostic relevance, and functional impact of PLEK2 across multiple cancer types. Using data from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), and the Human Protein Atlas, we analyzed PLEK2 expression in both cancerous and normal tissues, revealing significant overexpression of PLEK2 in various cancers at the mRNA and protein levels. Single-cell RNA sequencing further indicated predominant expression of PLEK2 in tumor cells and macrophages within the tumor microenvironment. Survival analysis demonstrated that elevated PLEK2 expression correlated with poor prognosis in specific cancers, though its impact varied across cancer types. Functional assays showed that PLEK2 knockdown inhibited proliferation and migration in human cancer cell lines. In vivo studies using a Lewis lung carcinoma (LLC) model confirmed that PLEK2 knockdown suppressed tumor growth and enhanced the efficacy of PD-1 immunotherapy. Mechanistically, PLEK2 knockdown was associated with reduced AKT pathway activation, diminished tumor-associated macrophage infiltration, and increased CD8 T cell presence. Compounds like Navitoclax were also identified as potential PLEK2 inhibitors. In conclusion, PLEK2 played a multifaceted role in cancer progression and immune response modulation. Targeting PLEK2 might suppress tumor growth and overcome immunotherapy resistance, offering a promising biomarker and therapeutic target to improve cancer treatment outcomes.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"59"},"PeriodicalIF":6.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy. XAF1 通过组装 ZNF313 介导的破坏复合物来拮抗 TRIM28 的活性，从而抑制肿瘤的恶性发展。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-13 DOI: 10.1186/s43556-024-00224-9

Seung-Hun Jang, Hwi-Wan Choi, Jieun Ahn, Sungchan Jang, Ji-Hye Yoon, Min-Goo Lee, Sung-Gil Chi

{"title":"XAF1 antagonizes TRIM28 activity through the assembly of a ZNF313-mediated destruction complex to suppress tumor malignancy.","authors":"Seung-Hun Jang, Hwi-Wan Choi, Jieun Ahn, Sungchan Jang, Ji-Hye Yoon, Min-Goo Lee, Sung-Gil Chi","doi":"10.1186/s43556-024-00224-9","DOIUrl":"10.1186/s43556-024-00224-9","url":null,"abstract":"X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a stress-inducible pro-apoptotic protein that is commonly inactivated in multiple human cancers. Nevertheless, the molecular basis for its tumor suppression function remains largely uncharacterized. Here we report that XAF1 antagonizes the oncogenic activity of tripartite motif containing 28 (TRIM28) ubiquitin E3 ligase through zinc finger protein 313 (ZNF313)-induced ubiquitination and proteasomal degradation. XAF1 exerts apoptosis-promoting effect more strongly in TRIM28+/+ versus XAF1-/- tumor cells and suppresses tumor cell growth, migration, invasion, and epithelial-to-mesenchymal transition and xenograft tumor growth in a highly TRIM28-dependent fashion. Mechanistically, XAF1 interacts directly with the RING domains of TRIM28 and ZNF313 through the ZF6 and ZF7 domain, respectively, thereby facilitating ZNF313 interaction with and ubiquitination of TRIM28. A mutant XAF1 lacking either ZF6 or ZF7 domain exhibits no activity to promote TRIM28 ubiquitination. By destabilizing TRIM28, XAF1 blocks TRIM28-driven ubiquitination of p53 and RLIM, p53-HDAC1 interaction, and TWIST1 stabilization. Intriguingly, TRIM28 destabilizes XAF1 through K48-linked polyubiquitination and proteasomal degradation to protect tumor cells from apoptotic stress, indicating its role as an intrinsic antagonist against XAF1 and the antagonistic interplay of XAF1 and TRIM28. XAF1 expression is inversely correlated with TRIM28 expression in cancer cell lines and tumor tissues and more tightly associated with the survival of TRIM28-high versus TRIM28-low patients. Together, this study uncovers a novel mechanism by which XAF1 suppresses tumor malignancy and an important role for XAF1-TRIM28 interplay in governing stress response, illuminating the mechanistic consequence of its alteration during tumorigenic process.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"58"},"PeriodicalIF":6.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteogenomics identifies c-Met inhibition as a therapeutic strategy for BAP1-deficient clear cell renal cell carcinoma. 蛋白质基因组学发现 c-Met 抑制是治疗 BAP1 缺陷透明细胞肾细胞癌的一种策略。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-12 DOI: 10.1186/s43556-024-00220-z

Bowen Du, Yulin Zhou, Wenzhi Li, Haowei He, Ming Chen, Ninghan Feng

引用次数: 0

Prophylactic and therapeutic vaccine development: advancements and challenges. 预防性和治疗性疫苗开发：进步与挑战。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-11 DOI: 10.1186/s43556-024-00222-x

Induni Nayodhara Weerarathna, Elijah Skarlus Doelakeh, Lydia Kiwanuka, Praveen Kumar, Sanvi Arora

{"title":"Prophylactic and therapeutic vaccine development: advancements and challenges.","authors":"Induni Nayodhara Weerarathna, Elijah Skarlus Doelakeh, Lydia Kiwanuka, Praveen Kumar, Sanvi Arora","doi":"10.1186/s43556-024-00222-x","DOIUrl":"10.1186/s43556-024-00222-x","url":null,"abstract":"Biomedical research is fundamental in developing preventive and therapeutic vaccines, serving as a cornerstone of global public health. This review explores the key concepts, methodologies, tools, and challenges in the vaccine development landscape, focusing on transitioning from basic biomedical sciences to clinical applications. Foundational disciplines such as virology, immunology, and molecular biology lay the groundwork for vaccine creation, while recent innovations like messenger RNA (mRNA) technology and reverse vaccinology have transformed the field. Additionally, it highlights the role of pharmaceutical advancements in translating lab discoveries into clinical solutions. Techniques like CRISPR-Cas9, genome sequencing, monoclonal antibodies, and computational modeling have significantly enhanced vaccine precision and efficacy, expediting the development of vaccines against infectious diseases. The review also discusses challenges that continue to hinder progress, including stringent regulatory pathways, vaccine hesitancy, and the rapid emergence of new pathogens. These obstacles underscore the need for interdisciplinary collaboration and the adoption of innovative strategies. Integrating personalized medicine, nanotechnology, and artificial intelligence is expected to revolutionize vaccine science further. By embracing these advancements, biomedical research has the potential to overcome existing challenges and usher in a new era of therapeutic and prophylactic vaccines, ultimately improving global health outcomes. This review emphasizes the critical role of vaccines in combating current and future health threats, advocating for continued investment in biomedical science and technology.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"57"},"PeriodicalIF":6.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer. 宫颈阴道灌洗发现生长因子是早期诊断和预后子宫内膜癌的关键生物标志物。

IF 5.3

Molecular biomedicine Pub Date : 2024-11-08 DOI: 10.1186/s43556-024-00219-6

Hannah J Harris, Paweł Łaniewski, Haiyan Cui, Denise J Roe, Dana M Chase, Melissa M Herbst-Kralovetz

{"title":"Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer.","authors":"Hannah J Harris, Paweł Łaniewski, Haiyan Cui, Denise J Roe, Dana M Chase, Melissa M Herbst-Kralovetz","doi":"10.1186/s43556-024-00219-6","DOIUrl":"10.1186/s43556-024-00219-6","url":null,"abstract":"Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05-0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"55"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T cell receptor repertoire characteristics and therapeutic potential of tumor infiltrating lymphocytes (TILs) derived from metastatic lymph node in cervical cancer. 来自宫颈癌转移淋巴结的肿瘤浸润淋巴细胞（TILs）的T细胞受体谱系特征和治疗潜力。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-04 DOI: 10.1186/s43556-024-00215-w

Xuan Zhao, Zhenjiang Liu, Haifeng Qin, Yarong Liu, Yi Zhang

引用次数: 0

Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model. 带装饰素的溶瘤腺病毒可促进自然杀伤因子（NKs）的激活和浸润，从而增强对 CRC 模型的 NK 治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-01 DOI: 10.1186/s43556-024-00212-z

Xue Li, Yuning Zhang, Zhuang Mao, Huiqiang Zhao, Hu Cao, Jingyi Wang, Wei Liu, Shiyun Dai, Yuefeng Yang, Yuanyuan Huang, Hua Wang

{"title":"Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model.","authors":"Xue Li, Yuning Zhang, Zhuang Mao, Huiqiang Zhao, Hu Cao, Jingyi Wang, Wei Liu, Shiyun Dai, Yuefeng Yang, Yuanyuan Huang, Hua Wang","doi":"10.1186/s43556-024-00212-z","DOIUrl":"10.1186/s43556-024-00212-z","url":null,"abstract":"Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"48"},"PeriodicalIF":6.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation. 纤维蛋白原的翻译后修饰：对凝血、纤维蛋白结构和降解的影响。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-31 DOI: 10.1186/s43556-024-00214-x

Francesca Nencini, Alessandra Bettiol, Flavia Rita Argento, Serena Borghi, Elvira Giurranna, Giacomo Emmi, Domenico Prisco, Niccolò Taddei, Claudia Fiorillo, Matteo Becatti

{"title":"Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation.","authors":"Francesca Nencini, Alessandra Bettiol, Flavia Rita Argento, Serena Borghi, Elvira Giurranna, Giacomo Emmi, Domenico Prisco, Niccolò Taddei, Claudia Fiorillo, Matteo Becatti","doi":"10.1186/s43556-024-00214-x","DOIUrl":"10.1186/s43556-024-00214-x","url":null,"abstract":"Fibrinogen, a blood plasma protein with a key role in hemostasis and thrombosis, is highly susceptible to post-translational modifications (PTMs), that significantly influence clot formation, structure, and stability. These PTMs, which include acetylation, amidation, carbamylation, citrullination, dichlorination, glycation, glycosylation, guanidinylation, hydroxylation, homocysteinylation, malonylation, methylation, nitration, oxidation, phosphorylation and sulphation, can alter fibrinogen biochemical properties and affect its functional behavior in coagulation and fibrinolysis. Oxidation and nitration are notably associated with oxidative stress, impacting fibrin fiber formation and promoting the development of more compact and resistant fibrin networks. Glycosylation and glycation contribute to altered fibrinogen structural properties, often resulting in changes in fibrin clot density and susceptibility to lysis, particularly in metabolic disorders like diabetes. Acetylation and phosphorylation, influenced by medications such as aspirin, modulate clot architecture by affecting fiber thickness and clot permeability. Citrullination and homocysteinylation, although less studied, are linked to autoimmune conditions and cardiovascular diseases, respectively, affecting fibrin formation and stability. Understanding these modifications provides insights into the pathophysiology of thrombotic disorders and highlights potential therapeutic targets. This review comprehensively examines the current literature on fibrinogen PTMs, their specific sites, biochemical pathways, and their consequences on fibrin clot architecture, clot formation and clot lysis.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"45"},"PeriodicalIF":6.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systemic lupus erythematosus: pathogenesis and targeted therapy. 系统性红斑狼疮：发病机制和靶向治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-30 DOI: 10.1186/s43556-024-00217-8

Xu Su, Hui Yu, Qingqiang Lei, Xuerui Chen, Yanli Tong, Zhongyang Zhang, Wenyong Yang, Yuanbiao Guo, Liangbin Lin

{"title":"Systemic lupus erythematosus: pathogenesis and targeted therapy.","authors":"Xu Su, Hui Yu, Qingqiang Lei, Xuerui Chen, Yanli Tong, Zhongyang Zhang, Wenyong Yang, Yuanbiao Guo, Liangbin Lin","doi":"10.1186/s43556-024-00217-8","DOIUrl":"10.1186/s43556-024-00217-8","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress and status of traditional and emerging treatment strategies for SLE. Traditional treatment strategies for SLE have mainly employed non-specific approaches, including cytotoxic and immunosuppressive drugs, antimalarials, glucocorticoids, and NSAIDs. These strategies are effective in mitigating the effects of the disease, but they are not a complete cure and are often accompanied by adverse reactions. Emerging targeted therapeutic drugs, on the other hand, aim to control and treat SLE by targeting B and T cells, inhibiting their activation and function, as well as the abnormal activation of the immune system. A deeper understanding of the pathogenesis of SLE and the exploration of new targeted treatment strategies are essential to advance the treatment of this complex autoimmune disease.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"54"},"PeriodicalIF":6.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The functions of apolipoproteins and lipoproteins in health and disease. 脂蛋白和脂蛋白在健康和疾病中的功能。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-28 DOI: 10.1186/s43556-024-00218-7

Zijun Ma, Jixin Zhong, Wei Tu, Shiliang Li, Jun Chen

{"title":"The functions of apolipoproteins and lipoproteins in health and disease.","authors":"Zijun Ma, Jixin Zhong, Wei Tu, Shiliang Li, Jun Chen","doi":"10.1186/s43556-024-00218-7","DOIUrl":"10.1186/s43556-024-00218-7","url":null,"abstract":"Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"53"},"PeriodicalIF":6.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0